ebn-ncm 4th yr

8/6/2019 ebn-ncm 4th yr

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I. Clinical Question:

Are men more likely to be at risk than women to

have colon cancer?


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II. Citation:

Sex-Specific Differences in Colon Cancer

Associated With p53 Mutations

REFERENCE:

http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=da9f6c12-2e0b-4267-a51a9834cbbd5e42%40sessionmgr112&vid=1&hid=112


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III. Study Characteristics

a. Patient included

Study participants were African American, white, orHispanic and were from the Kaiser PermanenteMedical Care Program (KPMCP) of northernCalifornia, an eight county area in Utah (Davis, SaltLake, Utah, Weber, Wasatch, Tooele, Morgan, andSummit counties), or the Twin Cities metropolitanarea in Minnesota. The study population wasapproximately 90% non-Hispanic white, 5% African

American, and 5% Hispanic.


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Subject Selection

Inclusion CriteriaEligibility criteria for cases included diagnosis withfirst-primary incident colon cancer (ICD-O, 2nd ed.,codes 18.0 and 18.218.9) between October 1, 1991,and September 30, 1994; between 30 and 79 yr ofage at time of diagnosis; and mentally competent tocomplete the interview.

Exclusion Criteria

Cases with adenocarcinoma or carcinoma of therectosigmoid junction or rectum (defined as the first15 cm from the anal opening) with known familialadenomatous polyposis, ulcerative colitis, or Crohnsdisease were not eligible.


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b. Interventions comparedThe study doesnt show any intervention to becompared. However in this study, theresearchers evaluate sex-specific associations

with acquiredp53 mutations in colon tumors byexamining both estrogen- and insulin-related

variables.


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c. Outcome monitored

Sex-specific differences in

observed incidence rates, tumor

subsite, and diet and lifestyle

associations with colon cancerhave been observed. The study

evaluates sex-specific

associations with p53 mutations

in colon cancer to add tounderstanding of these

differences.


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d. Does the study focus in significant

problem in clinical practice?

Yes, the study focuses on a significant problemin clinical practice because cancer is known as

one of the major cause of death in the world


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IV. Methodology/Design

Data were collected by trained and certified interviewersusing laptop computers. The referent period for the study was

the calendar year, approximately 2 year prior to date of diagnosis or date of interview for controls. Using this referentperiod, information was collected on dietary intake using adetailed diet history questionnaire. Methods for obtainingtumor tissue have been described. Colon cancer tissue was

micro dissected and DNA was extracted from formalin-fixedparaffin-embedded tissue blocks as described. Exons58 of -53 and relevant intron/exon boundaries were polymerasechain reaction (PCR) amplified with the primers.


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All tumor samples corresponding to any abnormally

migrating SSCP bands were reamplified with therespective primers tailed with UP and RP (andwithout dye labeling) for sequencing. PCR productswere sequenced using prism Big Dye terminatorsand cycle sequencing with Taq FS DNA polymerase.DNA sequence was collected and analyzed on an ABI

prism 377 automated DNA sequencer. Any alterations were verified by sequencing in bothdirections. SSCP was also performed on therespective germ line DNA sample of any tumor witha nonhot-spot missense mutation, insertion or

deletion mutations that consisted of multiples ofthree bases, and splice-site mutations to verify thatit was an acquired rather than inherited mutation.Sex-specific associations with acquired p53mutations were evaluated by examining age, tumor

site, and estrogen- related factors.


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Design

Data from a large population-based incidentcase-control study of colon cancer were used toevaluate age and gender associations with p53mutations. To obtain a better understanding of

gender- specific associations, we evaluated therole of estrogen as a mediator of risk. For theseanalyses, women were classified as estrogenpositive or negative, based on menopausal statusand use of hormone replacement therapy (HRT).

SettingNorthern California


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Has the original study been replicated?No, the study is original and has not been replicated.

What were the risks and benefits of the nursing

action/intervention tested in the study?

Observations that hormone replacement therapy (HRT) reducesrisk of colorectal cancer provide a biological basis for some of theobserved sex-specific differences in colorectal cancer reported .Sex-specific associations have been attributed to many factors,including the effect of estrogen on tumor development anddifferences in gut metabolism observed for men and women.Benefit from the study is the ability to examine tumors thatunravel our understanding of colon cancer by allowing us toobserve unique diet and lifestyle associations with specific tumorcharacteristics


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RESULT of STUDY

There was a significant interaction between age and sexand risk of an acquired p53 mutation compared with p53

Wt. Among men, there was an increase in p53 mutationswith age, whereas among women the opposite wasobserved. Associations with parity, oral contraceptive use,and total ovulatory months were not associated with p53mutations. However, recent use of HRT reduced risk of alltumors, as did being estrogen positive. Women who were

estrogen positive (either premenopausal or recent users ofHRT) were at a significantly increased risk of an acquiredp53 mutation if they consumed a diet with a high sugarindex (odds ratio = 2.94; 95% confidence interval = 1.475.89); similar increases in risk of p53 mutations were notobserved for men or women who were estrogen negative.


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Authors Contributions/Recommendations

Although sex-specific associations were detected foracquired p53 mutations, they do not indicate a

unique role of estrogens in the mutation of p53.These data are consistent with a role for estrogen inaltering susceptibility to diet and lifestyle factorspossibly via an insulin-related mechanism. Sex-specific associations with colon cancer have been

repeatedly observed. Men have higher incidencerates of colon cancer; women have more proximaltumors than men; and women have an increasedrisk of polyp recurrence on a high-carbohydrate diet,

whereas men do not.


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Observations that hormone replacement therapy

(HRT) reduces risk of colorectal cancer provide abiological basis for some of the observed sex-specific differences in colorectal cancer reported .Sex-specific associations have been attributed to

many factors, including the effect of estrogen ontumor development and differences in gutmetabolism observed for men and women. Abilityto examine tumors is helping to unravel ourunderstanding of colon cancer by allowing us toobserve unique diet and lifestyle associations withspecific tumor characteristics. Our recent work andthat by others suggest that estrogens may protectagainst tumors with microsatellite instability (MSI).


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This observation helps to explain both patterns ofMSI in tumors and possibly tumor subsitedifferences between men and women .Associations

between p53 immunohistochemistry-positivetumors and oral contraceptive use also have been

reported (12). Dietary glycemic index (GI) has beenreported as being more strongly associated with p53mutations in women than in men (13). Takentogether, this may suggest that estrogen-relatedfactors are associated with acquired p53 mutations.Explanations that account for both steroid (that is,estrogen) and growth hormones (that is, insulin)may better integrate the role of established riskfactors. Body size is related to a variety of metabolicphenomena that may influence cellularproliferation.


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A large body mass index (BMI) is associated withboth insulin resistance and alterations in estrogenmetabolism and function (14,15). Likewise, physicalactivity appears to play an important role in theregulation of both estrogen and insulin (16,17). In

this article, we evaluate sex-specific associationswith acquired p53 mutations in colon tumors byexamining both estrogen-and insulin-related

variables. We hypothesize that estrogen isassociated with p53 mutations that may involve

regulation of insulin-related mechanisms. Physicalactivity, BMI, and dietary sugar may be furthermodified by estrogen as they relate to p53 tumormutations.


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V. Applicability

a.) Does the study provide a direct enoughanswer to your clinical question in terms of

type of patients, intervention and outcome?The study had and answered the clinical questionadequately. With regards to the patients, Acquiredp53mutations were detected in 48.4% of colon tumors inmen and in 45.4% of colon tumors in women .Asignificant difference in age was observed for men and

women when comparing those with ap53 mutation withthose whose tumor did not have ap53 mutationtherefore answering the question that Sexes specificallydiffers in colon cancer associated with p53 mutations.


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b.) Is it feasible to carry out the nursingaction in the world?

Yes, with the understanding of the difference of

occurrence of colon cancer with p53 mutationsbetween sexes it can really help us nurses to beknowledgeable about patients who are mostprone of having colon cancer when it comes to

specific sexes.


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Reviewers Conclusion/Commentary

The study shows that men are more likely to havecolon cancer than women. As a conclusion, we can

say that this study does not only give us the ideaabout cancer but it also gives us the idea on how wecan prevent it from occurring to our life. This studycan also set as an eye-opener to everyone about thedifferent causes of cancer. However, even though

the study shows that men more likely to have coloncancer women should not be too confident becausethe percentage difference between the two gendersare not large meaning women are still at risk if theyare not going to take good care of their body.


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Evaluating Nursing Care

Process


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All patients chosen in the study are mentally

competent to finish the interview. Researchersfound out that old men are more at risk in coloncancer than old women. In addition, theyhypothesized that longer exposure to estrogen

and high sugar diet could lead to colon canceramong women. Use of Hormone ReplacementTherapy decreases risk to colon cancer among

women.

Safety


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The study used a test that determines theetiology of the cancer of the patient. It helps thepatient to watch what diet or lifestyle is

appropriate associated to their cancer.


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Data were collected by trained and certifiedinterviewers; and are technologically proficient.Specialized surgeons take the tumor tissues for

biopsy, and medical technologists interpret theresults.

Competence of theHealth care provider


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The study evaluates sex-specific associations with

mutations in colon cancer to add to understanding of thedifferences. Data from a large population-based incidentcase-control study of colon cancer were used to evaluateage and gender associations with mutations. To obtain a

better understanding of gender-specific associations, weevaluated the role of estrogen as a mediator of risk.

Acquired mutations were detected in 48.4% of colontumors in men and in 45.4% of colon tumors in women.Intervention used is suitable to the patients situationand acceptable to use to provide therapeutic effect onpatients.

Acceptability


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Interventions used, time and setting areappropriate to the patients. Study participants

were African American, white, or Hispanic andwere from the Kaiser Permanente Medical CareProgram (KPMCP) of northern California.

Knowledge on the proper treatment is necessaryin order to provide care that is acceptable andappropriate for both the nursing actions andclient

Appropriateness


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The study was safe and convenient for thepatients. And it is helpful based from the fact

that they got the knowledge to avoid what causetheir cancer.


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